Allergic diseases such as atopic dermatitis are considered multifactorial diseases. These diseases are caused by the interaction of many different genes whose expression is independently influenced by multiple environmental factors. Thus, determination of specific genes causing a specific disease has been extremely difficult for allergic diseases.
Furthermore, the expression of mutated or defective genes or overexpression or reduced expression of specific genes is assumed involved in allergic diseases. Therefore, to elucidate the role of gene expression in diseases, it is necessary to understand how a gene is involved at the onset of a disease and how the expression of the gene is altered by external stimulants such as drugs.
Recent developments in gene expression analysis techniques have enabled analysis and comparison of gene expression of many clinical samples. Among these methods, the differential display (DD) method is useful. Liang and Pardee originally developed this method in 1992 (Science, 1992, 257: 967–971). According to this method, several tens or more different samples can be screened at one time to detect genes whose expressions are different among the samples. Important information to reveal the causative gene of a disease is expected to be obtained by examining genes with mutations or genes whose expression changes depending on the time and environment. Such genes include those whose expression is influenced by environmental factors.
Medical examination by interview with the patient, confirmation of family history and anamnesis of the patient are generally important for recent diagnosis of allergic diseases. Furthermore, methods of diagnosing allergies based on information that is more objective include a method in which patient's blood sample is tested and a method of observing patient's immune response to allergen. Examples of the former method are the allergen-specific IgE measurement, leukocyte histamine release test and lymphocyte blast transformation test. The presence of allergen-specific IgE verifies the allergic reaction against the allergen. However, allergen-specific IgE is not always detected in every patient. Furthermore, the principle of IgE assay requires performing tests for all of the allergens necessary for diagnosis. The leukocyte histamine release test and lymphocyte blast transformation test are methods for observing the reaction of the immune system toward a specific allergen in vitro. These methods require complex operation.
Another known method for allergy diagnosis is based on the immune response observed at the time when a patient contacts an allergen (latter method). Such tests include the prick test, scratch test, patch test, intradermal reaction and induction test. These tests allow direct diagnosis of a patient's allergic reaction, but are highly invasive tests because the patients are actually exposed to allergen.
In addition, regardless of the allergen types, methods to confirm the involvement of an allergic reaction are also attempted. For example, a high serum IgE titer indicates the occurrence of allergic reaction in a patient. The serum IgE titer corresponds to the total amount of allergen-specific IgE. Though it is easy to determine the total amount of IgE regardless of the type of allergen, IgE titer may be reduced in some patients, for example, those with non-atopic bronchitis.
The number of eosinophils and eosinophil cationic protein (ECP) levels are diagnostic items for delayed-type reaction following Type I allergy and allergic inflammatory reaction. The number of eosinophils is considered to reflect the progress of allergic symptoms. ECP, a protein contained in eosinophil granules, is also strongly activated in patients with an asthma attack. Indeed, symptoms of allergies can be identified using these diagnostic items. However, only limited range of values can be used as a diagnostic index.
Therefore, diagnostic indices, regardless of the type of allergen, useful in comprehending pathological conditions of allergic disease patients and for determining the treatment regimen for the disease have been greatly needed in the art. Markers for allergic disease that are not only less harmful to patients but also capable of readily providing information required for diagnosis would be of great use. Identification of genes associated with allergic diseases enables tests for allergic diseases via the use of the expression of the genes as indexes. Furthermore, elucidation of the function of proteins encoded by the genes at the cell level is expected to promote, based on findings relating to their function, development of therapeutic methods and pharmaceutical agents for treating allergic diseases.